The long term objective of laboratory research on the role of micronutrients in immunomodulation and cancer prevention is the development of a scientifically-based dietary supplement which can be added to clinical resources for the prevention or treatment of cancer in humans. It is hoped the proposed studies will provide important clues for helping to better design human intervention studies researching the anticancer benefits of micronutrients on retrovirus-induced diseases. The proposed research addresses important questions that involve the interaction of three research disciplines: nutrition, immunology, and cancer biology. Research will be conducted at the animal level, cellular level, and molecular level using biological, immunochemical, and biochemical techniques to evaluate the ability of the micronutrients, selenium and vitamin E, as single micronutrients or in combination, to modulate immune dysfunctions and tumor pathology in an avian retrovirus model system. The avian retrovirus, reticuloendotheliosis virus, is an acute leukemia virus that transforms immature lymphoid cells and causes a severe immune suppression and fatal lymphoma. The proposed studies are designed to: 1) determine if immune dysfunctions and tumor pathology induced by the retrovirus or by retrovirus-transformed, non-virus-producing tumor cells can be modified by micronutrient supplementation; 2) establish optimal regimens of micronutrient supplementation (dosage and timing) and identify the most effective chemical form of the micronutrients required for causing modifications; 3) investigate cellular and molecular mechanisms involved in previously identified micronutrient alterations of retrovirus-induced immune dysfunctions and tumorigenesis; 4) determine if micronutrient supplementation enhances cellular or humoral antitumor immune functions of the host by assessing the influence of the micronutrients on normal immune responses and the suppressed immune responses caused by retrovirus infection; 5) define the role nutritionally enhanced immune responses play in cancer prevention; and, 6) determine if micronutrients prevent cancer by altering the viability, proliferation potential, or differentiation status of the tumor cells.